Quantification of the major metabolites of bromhexine in human plasma using RRLC-MS/MS and its application to pharmacokinetics
文献类型：期刊论文
| 作者 | Liu, Jia ; Chen, Xiaoyan; Hu, Youhong; Cheng, Gang; Zhong, Dafang
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| 刊名 | JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
 |
| 出版日期 | 2010-04-06 |
| 卷号 | 51期号:5页码:1134-1141 |
| 关键词 | Bromhexine Metabolites RRLC-MS/MS Quantification Pharmacokinetics Human plasma |
| ISSN号 | 0731-7085 |
| DOI | 10.1016/j.jpba.2009.11.024 |
| 文献子类 | Article |
| 英文摘要 | (E)-4-hydroxydemethylbromhexine (E-4-HDMB) and (E)-3-hydroxydemethylbromhexine (E-3-HDMB) were found as major metabolites, while (Z)-4-hydroxydemethylbromhexine and (Z)-3-hydroxydemethylbromhexine as minor metabolites of bromhexine in human plasma. These compounds were identified in comparison with synthetic authentic samples. A sensitive and selective rapid resolution liquid chromatography tandem mass spectrometry (RRLC-MS/MS) method was developed to quantify the concentration of bromhexine and its two major metabolites (E-4-HDMB and E-3-HDMB) in human plasma. Following solid phase extraction, the analytes were separated on a Zorbax 1.8 mu m particle size reversed-phase C-18 column, using a gradient elution program with solvents consisting of 0.1% formic acid in acetonitrile and 0.1% formic acid in 5mM ammonium acetate at a flow rate of 0.7 mL/min. Detection was carried out with an Agilent 6460 triple-quadrupole mass spectrometer operated with an electrospray ionization source mode operated in the positive ion mode. The recovery of bromhexine, E-4-HDMB, E-3-HDMB, and internal standard (IS) was 63.1-70.9%, 60.5-68.4%, 57.0-63.5%, and 87.8%, respectively. The matrix factors of bromhexine, E-4-HDMB, E-3-HDMB, and IS were 89.9-96.7%, 89.6-94.8%, 90.4-91.4%, and 103%, respectively. After an oral administration of 8.0 mg bromhexine to five healthy male subjects, AUC(0-24h) values of bromhexine, E-4-HDMB, and E-3-HDMB were found to be 93.5 +/- 31.9, 34.0 +/- 14.5, and 15.8 +/- 6.89 ng h/mL, respectively; while C-max values were 24.6 +/- 5.16, 3.11 +/- 1.13, and 5.36 +/- 2.55 ng/mL, respectively. Plasma concentration of bromhexine, E-4-HDMB, and E-3-HDMB declined with t(1/2) which gave 3.6 +/- 0.5, 8.4 +/- 2.7, and 6.4 +/- 2.5 h, respectively. (C) 2009 Elsevier B.V. All rights reserved. |
| WOS关键词 | AMBROXOL |
| 资助项目 | National Basic Research Program of China[2009CB930300] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000273835100020 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278922]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Zhong, Dafang |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Jia,Chen, Xiaoyan,Hu, Youhong,et al. Quantification of the major metabolites of bromhexine in human plasma using RRLC-MS/MS and its application to pharmacokinetics[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2010,51(5):1134-1141. |
| APA | Liu, Jia,Chen, Xiaoyan,Hu, Youhong,Cheng, Gang,&Zhong, Dafang.(2010).Quantification of the major metabolites of bromhexine in human plasma using RRLC-MS/MS and its application to pharmacokinetics.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,51(5),1134-1141. |
| MLA | Liu, Jia,et al."Quantification of the major metabolites of bromhexine in human plasma using RRLC-MS/MS and its application to pharmacokinetics".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 51.5(2010):1134-1141. |
入库方式： OAI收割
来源：上海药物研究所
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